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https://www.readbyqxmd.com/read/28106328/on-the-influence-of-the-protonation-states-of-active-site-residues-on-ache-reactivation-a-qm-mm-approach
#1
Thomas Driant, Florian Nachon, Cyril Ollivier, Pierre-Yves Renard, Etienne Derat
Acetylcholinesterase (AChE) is an enzyme of the serine hydrolase superfamily and a mediator of the signal transmission at cholinergic synapses catalysing acetylcholine cleavage into an acetate and a choline. This enzyme is vulnerable to covalent inhibition by organophosphate compounds (like VX). The covalent inhibition of AChE does not revert spontaneously and in order to restore catalytic activity known reactivator compounds have limited action. Simulations of VX-inhibited AChE reactivation by pralidoxime, a classical reactivator, were performed by QM/MM...
January 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28078916/in-vivo-protection-studies-of-bis-quaternary-2-hydroxyimino-n-pyridin-3-yl-acetamide-derivatives-hnk-oximes-against-tabun-and-soman-poisoning-in-swiss-albino-mice
#2
P Kumar, D Swami, D P Nagar, K P Singh, J Acharya, H N Karade, R Yadav
The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28043418/the-effectiveness-of-patient-tailored-treatment-for-acute-organophosphate-poisoning
#3
Chih-Chuan Lin, Dong-Zong Hung, Hsien-Yi Chen, Kuang-Hung Hsu
BACKGROUND: To determine a new pralidoxime (PAM) treatment guideline based on the severity of acute organophosphate intoxication patients, APACHE II score, and dynamic changes in serum butyrylcholinesterase (BuChE) activity. METHODS: This is a randomization trial. All patients received supportive care measurements and atropinization. Each enrolled patient was treated with 2 gm PAM intravenously as the loading dose. The control group was treated according to the WHO's recommended PAM regimen, and the experimental group was treated according to their APACHE II scores and dynamic changes in BuChE activity...
December 2016: Biomedical Journal
https://www.readbyqxmd.com/read/28043415/pralidoxime-and-pesticide-poisoning-a-question-of-severity
#4
EDITORIAL
Emma Louise Walton
In this issue of the Biomedical Journal, we highlight new data supporting the use of pralidoxime in the treatment of cases of organophosphate poisoning, which also suggest that WHO treatment guidelines should be updated. We also learn about a modified surgical technique to repair severe spinal injuries, as well as new insight into the structure of human adenovirus that could inform vaccine development.
December 2016: Biomedical Journal
https://www.readbyqxmd.com/read/27990564/planarian-cholinesterase-in-vitro-characterization-of-an-evolutionarily-ancient-enzyme-to-study-organophosphorus-pesticide-toxicity-and-reactivation
#5
Danielle Hagstrom, Hideto Hirokawa, Limin Zhang, Zoran Radic, Palmer Taylor, Eva-Maria S Collins
The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D...
December 18, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27728587/pralidoxime-in-acute-organophosphate-poisoning-a-randomized-trial
#6
Bammigatti C, M Vinod Babu, T Kadhiravan, R P Swaminathan
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27651556/acute-poisoning-in-a-child-following-topical-treatment-of-head-lice-pediculosis-capitis-with-an-organophosphate-pesticide
#7
Muddathir H Hamad, Ahmed Awad Adeel, Ali Abdu N Alhaboob, Ahmed M Ashri, Mustafa A Salih
This is a case report of acute organophosphate poisoning in a child treated with topical application of Diazinon-60 (WHO Class II toxicity) for head lice (pediculosis capitis). The patient presented with neurological symptoms and signs. After emergency respiratory and circulatory resuscitation the patient underwent dermal decontamination and was treated with atropine, high flow oxygen and pralidoxime. Scanning electron micrographs of scalp hair specimens revealed both viable and empty head lice nits (lice eggs that attach to the hair shaft)...
2016: Sudanese Journal of Paediatrics
https://www.readbyqxmd.com/read/27432237/toxicity-and-median-effective-doses-of-oxime-therapies-against-percutaneous-organophosphorus-pesticide-and-nerve-agent-challenges-in-the-hartley-guinea-pig
#8
Thomas H Snider, Michael C Babin, David A Jett, Gennady E Platoff, David T Yeung
Anticholinesterases, such as organophosphorus pesticides and warfare nerve agents, present a significant health threat. Onset of symptoms after exposure can be rapid, requiring quick-acting, efficacious therapy to mitigate the effects. The goal of the current study was to identify the safest antidote with the highest therapeutic index (TI = oxime 24-hr LD50/oxime ED50) from a panel of four oximes deemed most efficacious in a previous study. The oximes tested were pralidoxime chloride (2-PAM Cl), MMB4 DMS, HLö-7 DMS, and obidoxime Cl2...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27418928/the-effect-of-parathion-on-red-blood-cell-acetylcholinesterase-in-the-wistar-rat
#9
Naofumi Bunya, Keigo Sawamoto, Hanif Benoit, Steven B Bird
Organophosphorus (OP) pesticide poisoning is a significant problem worldwide. Research into new antidotes for these acetylcholinesterase inhibitors, and even optimal doses for current therapies, is hindered by a lack of standardized animal models. In this study, we sought to characterize the effects of the OP pesticide parathion on acetylcholinesterase in a Wistar rat model that included comprehensive medical care. Methods. Male Wistar rats were intubated and mechanically ventilated and then poisoned with between 20 mg/kg and 60 mg/kg of intravenous parathion...
2016: Journal of Toxicology
https://www.readbyqxmd.com/read/27396356/in-vitro-characterization-of-pralidoxime-transport-and-acetylcholinesterase-reactivation-across-mdck-cells-and-stem-cell-derived-human-brain-microvascular-endothelial-cells-bc1-hbmecs
#10
Erin Gallagher, Il Minn, Janice E Chambers, Peter C Searson
BACKGROUND: Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. METHODS: To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs)...
July 11, 2016: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/27266642/-acute-poisoning-by-pesticides-in-children
#11
P Leveau
Acute pesticide poisoning in children is rare but potentially serious. Some clinical patterns (toxidromes) are suggestive of the drug class: cholinergic crisis for organophosphate or carbamate insecticides; neurological syndrome for rodenticides; digestive and respiratory syndrome for herbicides. Treatment is symptomatic and only a few patients are treated with an antidote: atropine and pralidoxime for organophosphate insecticides, vitamin K for anticoagulant rodenticides.
July 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/27179675/a-liquid-chromatography-tandem-mass-spectrometric-method-on-in-vitro-nerve-agents-poisoning-characterization-and-reactivator-efficacy-evaluation-by-determination-of-specific-peptide-adducts-in-acetylcholinesterase
#12
Long Yan, Jia Chen, Bin Xu, Lei Guo, Yan Xie, Jijun Tang, Jianwei Xie
The terroristic availability of highly toxic nerve agents (NAs) highlights the necessity for a deep understanding of their toxicities and effective medical treatments. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a characterization of the NAs poisoning and an evaluation on the efficacy of reactivators in in vitro was developed for the first time. After exposure to sarin or VX and pepsin digestion, the specific peptides of acetylcholinesterase (AChE) in a purified status, i.e. undecapeptide "GESAGAASVGM" in free, unaged, or aged status was identified and quantified...
June 10, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27158860/intramuscular-versus-intraosseous-delivery-of-nerve-agent-antidote-pralidoxime-chloride-in-swine
#13
Nabeel I Uwaydah, Stephen L Hoskins, Stephen P Bruttig, Henry Farrar, Nick C Copper, Donald J Deyo, Michael A Dubick, George C Kramer
OBJECTIVE: Exposure to nerve agents requires prompt treatment. We hypothesized that intraosseous (IO) injections of drug antidotes into the vascularized bone marrow will provide a more rapid and effective means to treat exposure to nerve agents than standard intramuscular (IM) injections. We compared the pharmacokinetics of IM and IO administration of pralidoxime chloride (2-PAM Cl) during normovolemia and hypovolemia, as well as their combined administration during normovolemia in swine...
July 2016: Prehospital Emergency Care
https://www.readbyqxmd.com/read/27125761/oximes-in-organophosphate-poisoning-60-years-of-hope-and-despair
#14
Franz Worek, Horst Thiermann, Timo Wille
The high number of annual fatalities following suicidal poisoning by organophosphorus (OP) pesticides and the recent homicidal use of the chemical warfare nerve agent sarin against civilian population in Syria underlines the continuous threat by these highly toxic agents. The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Since the invention of the first clinically used oxime pralidoxime (2-PAM) in the 1950s ongoing research attempted to identify more effective oximes...
November 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27102179/efficacy-of-recommended-prehospital-human-equivalent-doses-of-atropine-and-pralidoxime-against-the-toxic-effects-of-carbamate-poisoning-in-the-hartley-guinea-pig
#15
Matthew K Brittain, Kevin G McGarry, Robert A Moyer, Michael C Babin, David A Jett, Gennady E Platoff, David T Yeung
PURPOSE: Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning (muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride [2-PAM Cl]) could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates...
May 2016: International Journal of Toxicology
https://www.readbyqxmd.com/read/27062893/probing-the-activity-of-a-non-oxime-reactivator-for-acetylcholinesterase-inhibited-by-organophosphorus-nerve-agents
#16
C Linn Cadieux, Haoyu Wang, Yuchen Zhang, Jeffrey A Koenig, Tsung-Ming Shih, John McDonough, John Koh, Douglas Cerasoli
Currently fielded treatments for nerve agent intoxication include atropine, an acetylcholine receptor antagonist, and pralidoxime (2PAM), a small molecule reactivator of acetylcholinesterase (AChE). 2PAM reactivates nerve agent-inhibited AChE via direct nucleophilic attack by the oxime moiety on the phosphorus center of the bound nerve agent. Due to a permanently charged pyridinium motif, 2PAM is not thought to cross the blood brain barrier and therefore cannot act directly in the neuronal junctions of the brain...
November 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27014821/-the-influence-of-sodium-bicarbonate-combined-with-ulinastatin-on-cholinesterase-activity-for-patients-with-acute-phoxim-pesticide-poisoning
#17
RANDOMIZED CONTROLLED TRIAL
Bo Zhao, Lanju Yang, Lei Xiao, Baoquan Sun, Xianbao Zou, Dongmei Gao, Xiandong Jian
OBJECTIVE: To observe the effect of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning. METHODS: A total of 67 eligible patients with acute phoxim pesticide poisoning, Who were admitted to the emeryency department of hospital from March 2011 to February 2014, Acording to different treatments au patients were randomly divided into the conventional treatment group (n=34) and the sodium bicarbonate+ulinastatin group (n=35) ...
January 2016: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/26972668/an-easy-method-for-the-determination-of-active-concentrations-of-cholinesterase-reactivators-in-blood-samples-application-to-the-efficacy-assessment-of-non-quaternary-reactivators-compared-to-hi-6-and-pralidoxime-in-vx-poisoned-mice
#18
André-Guilhem Calas, José Dias, Catherine Rousseau, Mélanie Arboléas, Mélanie Touvrey-Loiodice, Guillaume Mercey, Ludovic Jean, Pierre-Yves Renard, Florian Nachon
Organophosphorus nerve agents, like VX, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). AChE inhibited by VX can be reactivated using powerful nucleophilic molecules, most commonly oximes, which are one major component of the emergency treatment in case of nerve agent intoxication. We present here a comparative in vivo study on Swiss mice of four reactivators: HI-6, pralidoxime and two uncharged derivatives of 3-hydroxy-2-pyridinaldoxime that should more easily cross the blood-brain barrier and display a significant central nervous system activity...
March 10, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/26962110/in-vivo-protection-studies-of-bis-quaternary-2-hydroxyimino-n-pyridin-3-yl-acetamide-derivatives-against-sarin-poisoning-in-mice
#19
Devyani Swami, Hitendra N Karade, Jyotiranjan Acharya, Pravin Kumar
In vivo antidotal efficacy of new bis- quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives (HNK series), to counter multiples of lethal doses of nerve agent sarin (GB) and reactivation of acetylcholinesterase (AChE), was evaluated in Swiss albino mice. [Protection index PI; median lethal dose (LD50) of sarin with treatment/LD50 of sarin] was estimated, using 0.05, 0.10, and 0.20 LD50 as treatment doses of all the oximes with atropine against sarin poisoning. Dose-dependent time course study was conducted at 0...
March 9, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/26887209/-transcutaneous-electrical-stimulation-undergoing-emergency-treatment-of-zusanli-st-36-is-beneficial-to-rescued-organophosphorus-pesticide-poisoning-patients
#20
RANDOMIZED CONTROLLED TRIAL
Hui Gao, Mai-liang Zhao, Ai-min Zhou, Sheng Zhang, Zhong-hai Song, Wen-ping Guo, Zhi-an Deng
OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) of Zusanli (ST 36) on gastrointestinal activities in organophosphorus pesticide poisoning (OPP) patients undergoing emergency treatment so as to explore its action in scavenging gastrointestinal toxicant. METHODS: A total of 116 OPP patients were randomly divided into control group and TAES group (n=58 in each group) according to the simple random sampling method. All the patients received comprehensive treatment including gastric lavage, catharsis, oral administration of atropine Pralidoxime Chloride, Omeprazole, etc...
December 2015: Zhen Ci Yan Jiu, Acupuncture Research
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